This project is to investigate the role of genes in aging, using Drosophila as a model system, in which the genes can be manipulated in various ways. One way is to screen for mutant genes that extend lifespan, as exemplified by the mutant methuselah, isolated in our laboratory. Since increased longevity is usually correlated with enhanced resistance to various forms of stress, screening for stress-resistant mutants is another approach to identifying life-assurance genes. A third approach is to identify genes whose expression is strongly increased in response to stress, then to determine whether overexpression of some such genes can extend lifespan. All these methods have provided candidate genes related to life extension. Chosen ones will be analyzed by molecular techniques to identify their tissue specificity of expression and their signal transduction and other cellular processes underlying aging, thus providing clues to roles in manipulation of specific gene expression that can contribute to enhanced, healthy lifespan.